Human Induced Pluripotent Stem Cells Derived From Adult And Fetal Hepatocytes For The Study And Treatment Of Liver Metabolic Diseases

Hepatocyte transplantation has been used to treat liver disease. The availability of cells for these procedures is quite limited. hESCs and hiPSCs may be a useful source of hepatocytes for basic research and transplantation if efficient and effective differentiation protocols were developed and problems with tumorigenicity could be overcome. Recent evidence suggests that the cell of origin may affect hiPSC differentiation. Thus, hiPSCs generated from hepatocytes may differentiate back to hepatocytes more efficiently than hiPSCs from other cell types. We examined the efficiency of reprogramming adult and fetal human hepatocytes. The present studies report the generation of 40 hiPSC lines from primary human hepatocytes under feeder-free conditions (37 from fetal hepatocytes, 2 from normal adult hepatocytes and 1 from adult hepatocytes of a patient with Crigler-Najjar Syndrome, Type-1). All lines were confirmed reprogrammed and expressed markers of pluripotency by gene expression, flow cytometry, immunofluorescence, and teratoma formation. Fetal hepatocytes were reprogrammed at a frequency over 50-fold higher than adult hepatocytes. Adult hepatocytes were only reprogrammed with 6 factors, while fetal hepatocytes could be reprogrammed with 3 or 4 factors. The increased reprogramming efficiency of fetal cells was not due to increased transduction efficiency or vector toxicity. We also report the transplantation and differentiation of human fetal hepatocyte-derived iPSCs. We show preliminary data that undifferentiated cells can engraft in mouse livers of FRG and NOD/SCID mice. Engraftment was based on human DNA presence in liver tissue. Furthermore we differentiated these cells to definitive endoderm and transplanted them to FRG mice. Human DNA and human albumin were present in mouse livers and mouse serum respectively. Finally, full hepatic differentiation was performed, although we show limited results in terms of the cells’ ability to express liver specific genes and perform liver-specific metabolism. Taken together, these studies confirm that hiPSCs can be generated from adult and fetal hepatocytes, including those with genetic diseases, and differentiated back to the hepatocyte lineage. Fetal hepatocytes reprogram much more efficiently than adult, although both could serve as useful sources of hiPSC-derived hepatocytes for basic research or transplantation if an efficient hepatic differentiation protocol could be developed

I. Observations on the Straits of Malacca, in regard to natural history, geography, and commerce

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Temperature effects on the magnetization of quasi-one-dimensional Peierls distorted materials

It is shown that temperature acts to disrupt the magnetization of Peierls distorted quasi-one-dimensional materials (Q1DM). The mean-field finite temperature phase diagram for the field theory model employed is obtained by considering both homogeneous and inhomogeneous condensates. The tricritical points of the second order transition lines of the gap parameter and magnetization are explicitly calculated. It is also shown that in the absence of an external static magnetic field the magnetization is always zero, at any temperature. As expected, temperature does not induce any magnetization effect on Peierls distorted Q1DM.Comment: 11 pages, 2 figure

A Moving Bump in a Continuous Manifold: A Comprehensive Study of the Tracking Dynamics of Continuous Attractor Neural Networks

Understanding how the dynamics of a neural network is shaped by the network structure, and consequently how the network structure facilitates the functions implemented by the neural system, is at the core of using mathematical models to elucidate brain functions. This study investigates the tracking dynamics of continuous attractor neural networks (CANNs). Due to the translational invariance of neuronal recurrent interactions, CANNs can hold a continuous family of stationary states. They form a continuous manifold in which the neural system is neutrally stable. We systematically explore how this property facilitates the tracking performance of a CANN, which is believed to have clear correspondence with brain functions. By using the wave functions of the quantum harmonic oscillator as the basis, we demonstrate how the dynamics of a CANN is decomposed into different motion modes, corresponding to distortions in the amplitude, position, width or skewness of the network state. We then develop a perturbative approach that utilizes the dominating movement of the network's stationary states in the state space. This method allows us to approximate the network dynamics up to an arbitrary accuracy depending on the order of perturbation used. We quantify the distortions of a Gaussian bump during tracking, and study their effects on the tracking performance. Results are obtained on the maximum speed for a moving stimulus to be trackable and the reaction time for the network to catch up with an abrupt change in the stimulus.Comment: 43 pages, 10 figure

Caracterização química de quatro espécies de eucalipto para produção de bioetanol.

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Miniaturização da análise de açúcares livres em tecido foliar pelo método de fenol-ácido sulfúrico.

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Titulação potenciométrica como alternativa para determinação direta e simultânea de Ca+2 e Mg+2 em solos.

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Introdução ao cultivo in vitro de Guanandi (Calophyllum brasiliense Camb.) oriundos de Morretes e Paranaguá, PR.

EVINCI. Resumo 003

Estabelecimento e multiplicação in vitro do guanandi (Calophyllum brasiliense).

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